Venous thromboembolism, comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major contributor to morbidity and mortality in the United States. Nevertheless, no comprehensive, prospective, population-based epidemiologic studies have simultaneously examined lifestyle, molecular, and biochemical risk factors for this important disease. The proposed project will efficiently investigate venous thromboembolism in two carefully conducted prospective epidemiologic studies of African American and white adults -- the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). The aims are as follow: 1) to identify and validate DVT and PE cases, in order to estimate incident rates of hospitalized venous thromboembolism in the combined ARIC and CHS cohorts; 2) to determine prospectively the association of venous thromboembolism with demographic and lifestyle factors, plasma lipids, medical history, and hemostatic components (including fibrinogen, platelet count, factors VIIc and VIIIc) using existing ARIC and CHS data; and 3) to conduct a nested case control study using stored pre-diagnosis blood and DNA specimens to determine the prospective associations of venous thromboembolism with the following: levels of procoagulant or anticoagulant factors and related genetic variants (including factor V Leiden), fibrinolytic factors (e.g., plasminogen activator inhibitor-1) and related genetic variants, markers of thrombin activation, and other potentially important biochemical or related genetic factors (e.g., homocysteine). The investigators point out that the concurrent measurement of these lifestyle, molecular, and biochemical factors, and estimation of their relative and attributable risks in a comprehensive prospective study, will provide important epidemiologic insights into the etiology of venous thromboembolism.